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ABSTRACT The ability of cells to sense and respond to mechanical signals is essential for many biological processes that form the basis of cell identity, tissue development and maintenance. This process, known as mechanotransduction, involves crucial feedback between mechanical force and biochemical signals, including epigenomic modifications that establish transcriptional programs. These programs, in turn, reinforce the mechanical properties of the cell and its ability to withstand mechanical perturbation. The nucleus has long been hypothesized to play a key role in mechanotransduction due to its direct exposure to forces transmitted through the cytoskeleton, its role in receiving cytoplasmic signals and its central function in gene regulation. However, parsing out the specific contributions of the nucleus from those of the cell surface and cytoplasm in mechanotransduction remains a substantial challenge. In this Review, we examine the latest evidence on how the nucleus regulates mechanotransduction, both via the nuclear envelope (NE) and through epigenetic and transcriptional machinery elements within the nuclear interior. We also explore the role of nuclear mechanotransduction in establishing a mechanical memory, characterized by a mechanical, epigenetic and transcriptomic cell state that persists after mechanical stimuli cease. Finally, we discuss current challenges in the field of nuclear mechanotransduction and present technological advances that are poised to overcome them.
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Nuclear Mechanics within Intact Cells Is Regulated by Cytoskeletal Network and Internal Nanostructures
Abstract The mechanical properties of the cellular nucleus are extensively studied as they play a critical role in important processes, such as cell migration, gene transcription, and stem cell differentiation. While the mechanical properties of the isolated nucleus have been tested, there is a lack of measurements about the mechanical behavior of the nucleus within intact cells and specifically about the interplay of internal nuclear components with the intracellular microenvironment, because current testing methods are based on contact and only allow studying the nucleus after isolation from a cell or disruption of cytoskeleton. Here, all‐optical Brillouin microscopy and 3D chemomechanical modeling are used to investigate the regulation of nuclear mechanics in physiological conditions. It is observed that the nuclear modulus can be modulated by epigenetic regulation targeting internal nuclear nanostructures such as lamin A/C and chromatin. It is also found that nuclear modulus is strongly regulated by cytoskeletal behavior through a robust mechanism conserved in different culturing conditions. Given the active role of cytoskeletal modulation in nearly all cell functions, this work will enable to reveal highly relevant mechanisms of nuclear mechanical regulations in physiological and pathological conditions.
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- Award ID(s):
- 1929412
- PAR ID:
- 10457734
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Small
- Volume:
- 16
- Issue:
- 18
- ISSN:
- 1613-6810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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